Carboxylic acid-stabilised iron oxide nanoparticles for use in magnetic hyperthermia

Abstract

Iron oxide nanoparticles were made in the presence of three carboxylic acid functionalised organic ligands (tiopronin, oxamic acid and succinic acid) using a co-precipitation method. The iron oxide was a mixture of magnetite and maghemite with an average crystallite size less than 10 nm. The samples were all dialysed prior to analysis to ensure high purity. Without the presence of a carboxylic acid, the dialysis purification stage invoked complete precipitation and the sample was completely intractable. The carboxylic acid stabilised particles could be dissolved in water to form a stable solution. The samples prepared with tiopronin and succinic acid were close to neutral pH and were suitable for magnetic fluid hyperthermia testing on Staphyloccocus aureus. Iron oxide produced with tiopronin was able to achieve a 10⁷-fold reduction in the viable count of the organism using a 2 × 2 minute exposure to an AC magnetic field and this bactericidal effect could still be achieved using the same batch of particles one week later. Oxidation of the samples did occur with aging or sonication and made the heating response less effective after one month. The tiopronin stabilised nanoparticles were able to achieve substantial kills of bacteria at concentrations between 6.25–50 mg/ml. This is, to our knowledge, the first time magnetic hyperthermia has been used to kill bacteria. The heating rates obtained from using an external magnetic alternating field on the iron oxide nanoparticle solutions were four times greater than the best commercially available material. This novel method of killing bacteria could form the basis of a new approach to the treatment of a variety of infectious diseases.